SUMMARY OF WORK With injury to the vessel wall (e.g. atherosclerosis or balloon angioplasty), the local release of growth factors and cytokines acts as a stimulus for smooth muscle cells to produce protein products, to migrate and to proliferate. Transcriptional pathways, shared by gamma-IFN, PDGF, and other cytokines and factors involved in the vascular response to injury or atherosclerosis, include members of the STAT family (signal transducer and activator of transcription) of transcription factors. STAT proteins become tyrosine phosphorylated directly or through JAK family kinases by plasma membrane receptors, translocates to the nucleus, and binds specific DNA sequences in gene promoter regions. We found that after balloon injury to the rat carotid artery, a neointima is formed that stained significantly for gamma-IFN. Further, we found when control and balloon injured carotid rat arteries ( 0 to 56 days after angioplasty) were compared that there was an increased expression of STAT1 and STAT3 proteins after balloon injury. STAT1 and STAT3 staining was most prominent in the neointimal cells surrounding the lumen of the vessel and coincided with areas of more intense IFN-[unreadable] staining. Previously, we found that gamma-IFN increased the expression of STAT1 in cultured rat vascular smooth muscle cells and, therefore, we propose that gamma-IFN present within these vascular lesions likewise may increase STAT1 protein expression. A combination of increased STAT expression and activation may lead to a different program of gene activation by the smooth muscle cells. We found that ICAM-1, an inflammatory cell adhesion molecule whose expression is controlled in part by STAT1, staining also correlated with increased STAT1 staining in neointimal cells. We also examined protein extracts from human aortas for changes in the expression of STAT1 and 3. Fresh aorta (6 to 18 hrs after death was obtained from an area trauma center) was characterized according to the severity of atherosclerotic lesions. The aortas were either fixed for subsequent immunostaining of STAT proteins or protein was extracted for Western analysis of expressed proteins. We found no clear relationship between the severity of atherosclerosis and the intensity of STAT1 and 3 staining in the Western blots. Immunostaining of formalin fixed aortas demonstrated both STAT1 and 3 staining of tissue, especially of endothelial cells, but there was no clear relationship between the type and severity of the atherosclerotic lesion and the intensity or location of STAT staining. Further studies of atherosclerotic lesions will focus on the cell types expressing increased STAT proteins to elucidate potential roles for STAT proteins in vascular pathophysiology or physiology.